Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurobehavioral diseases of children's age and is observed in 4-10% of children. Approximately in 50% of children diagnosed with ADHD have symptoms that persist into adulthood. Emotional restlessness, impulsive behavior and thought, lack of attention, inability to concentrate and focus, talking excessively, absent-mindedness, etc. are some of the symptoms of ADHD.
Neurotropic drugs having antiserum to brain-specific protein S-100 are known. (RU 2156621 C1, A61K39/395, Sep. 27, 2000). However, these medicines do not provide sufficient therapeutic efficiency for treatment of neurobehavioral diseases, including attention deficit hyperactivity disorder. Thus, there is a continuing need for new drug products with the desired therapeutic efficacy for the treatment of attention deficit hyperactivity disorder.
The therapeutic effect of an extremely diluted form (or ultra-low form) of antibodies potentized by homeopathic technology (activated-potentiated form) has been discovered by the inventor of the present patent application, Dr. Oleg I. Epshtein. U.S. Pat. No. 7,582,294 discloses a medicament for treating Benign Prostatic Hyperplasia or prostatitis by administration of a homeopathically activated form of antibodies to prostate specific antigen (PSA). U.S. Pat. No. 7,700,096 discloses a homeopathically potentized form of antibodies to endothelial NO-synthase.
The S-100 protein is a cytoplasmic acidic calcium binding protein found predominantly in the gray matter of the brain, primarily in glia and Schwann cells. The protein exists in several homo- or heterodimeric isoforms consisting of two immunologically distinct subunits, alpha and beta. The S-100 protein has been suggested for use as an aid in the diagnosis and assessment of brain lesions and neurological damage due to brain injury, as in stroke. Yardan et al., Usefulness of S100B Protein in Neurological Disorders, J Pak Med Assoc Vol. 61, No. 3, March 2011, which is incorporated herein by reference.
Ultra-low doses of antibodies to S-100 protein have been shown to have anxiolytic, anti-asthenic, anti-aggressive, stress-protective, anti-hypoxic, anti-ischemic, neuroprotective and nootropic activity. See Castagne V. et al., Antibodies to S100 proteins have anxiolytic-like activity at ultra-low doses in the adult rat, J Pharm Pharmacol. 2008, 60(3):309-16; Epstein O. I., Antibodies to calcium-binding S100B protein block the conditioning of long-term sensitization in the terrestrial snail, Pharmacol Biochem Behay., 2009, 94(1):37-42; Voronina T. A. et al., Chapter 8. Antibodies to S-100 protein in anxiety-depressive disorders in experimental and clinical conditions. In “Animal models in biological psychiatry”, Ed. Kalueff A. V. NY, “Nova Science Publishers, Inc.”, 2006, pp. 137-152, all of which are incorporated herein by reference.
Nitric oxide (NO) is a gaseous molecule that has been shown to acts in the signaling of different biological processes. Endothelium-derived NO is a key molecule in regulation of vascular tone and its association with vascular disease has long been recognized. NO inhibits many processes known to be involved in the formation of atherosclerotic plaque, including monocyte adhesion, platelet aggregation and vascular smooth muscle cell proliferation. Another important role of endothelial NO is the protection of the vascular wall from the oxidative stress induced by its own metabolic products and by the oxidation products of lipids and lipoproteins. Endothelial dysfunction occurs at very early stages of atherosclerosis. It is therefore possible that deficiency in local NO availability could be a final common pathway that accelerates atherogenesis in humans. In addition to its role in the vascular endothelium, NO availability has been shown to modulate metabolism of lipoproteins. Negative correlation has been reported between plasma concentrations of NO metabolic products and plasma total and Low Density Lipoprotein [LDL] cholesterol levels while High Density Lipoprotein [HDL] improves vascular function in hypercholesterolaemic subjects. The loss of NO has considerable effect on the development of the disease. Diabetes mellitus is associated with increased rates of morbidity and mortality caused primarily by the accelerated development of atherosclerotic disease. Moreover, reports show that diabetics have impaired lung functions. It has been proposed that insulin resistance leads to airway inflammation. Habib et al., Nitric Oxide Measurement From Blood To Lungs, Is There A Link? Pak J Physiol 2007; 3(1).
Nitric oxide is synthesized by the endothelium from L-arginine by nitric oxide synthase (NO synthase). NO synthase occurs in different isoforms, including a constitutive form (cNOS) and an inducible form (iNOS). The constitutive form is present in normal endothelial cells, neurons and some other tissues.